Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions

To understand how nanocarriers (NCs) distribute between inflamed vs. healthy tissue, we created a mouse model in which just one lobe of the lung is severely inflamed (inset photo). We found that highly lung-avid NCs (PECAM/NCs) preferentially accumulate in the healthy lung tissue, due to hypoxic vasoconstriction in the inflamed tissue. Surprisingly, untargeted NCs (IgG/NCs) accumulate in the inflamed tissue, due to capillary leak there. These experimental findings, along with computational modeling, allowed us to design a highly lung-avid NC that also preferentially targets the inflamed tissue.84